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Transcriptome analysis in brown adipose tissue of mice lacking ATF4 in thermogenic adipocytes.

ABSTRACT: Transcriptome analysis in brown adipose tissue of mice lacking ATF4 in thermogenic adipocytes.

PROVIDER: PRJNA942971 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23784473.fastq.gz	Fastqsanger.gz
	SRR23784474.fastq.gz	Fastqsanger.gz
	SRR23784475.fastq.gz	Fastqsanger.gz
	SRR23784476.fastq.gz	Fastqsanger.gz
	SRR23784477.fastq.gz	Fastqsanger.gz

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Transcriptome analysis in brown adipose tissue of mice lacking ATF4 in thermogenic adipocytes

Project description:Transcriptome analysis in brown adipose tissue of mice lacking ATF4 in thermogenic adipocytes

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Transcriptome analysis in brown adipose tissue of mice lacking ATF4 in thermogenic adipocytes.

Project description:mRNA expression profiles from interscapular brown adipose (iBAT) tissue male ATF4 BAT KO mice and their WT counterparts after 3 days of cold exposure.

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Transcriptome analysis in brown adipose tissue of mice lacking ATF4 in thermogenic adipocytes

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Project description:Sustained responses to transient stimuli are important for animals to survive and reproduce in their environment. However, the mechanisms that underlie altered responses to temporary shifts in abiotic factors, such as temperature, remain poorly understood. Here, we find that transient cold exposure leads to sustained transcriptional and metabolic adaptations in brown adipose tissue, which are critical for an improved thermogenic response to secondary cold encounter. Primary thermogenic challenge triggers the delayed induction of a lipid biosynthesis program even after cessation of the original stimulus, which protects from subsequent exposures. By combining single-nucleus RNA sequencing, spatial transcriptomics, and immunofluorescence imaging, we discover that this lipogenic response is carried out by a distinct subpopulation of brown adipocytes that is localized along the perimeter of classical Ucp1high brown adipocytes. The protective effect of the lipogenic program is associated with the production of acyl carnitines, and supplementation of acyl carnitines recapitulates improved secondary cold responses even in the absence of lipogenesis. Overall, our data highlight the importance of heterogenous brown adipocyte populations for “thermogenic memory” in the setting of repeated cold exposure, which may have implications for therapeutic efforts leveraging short-term thermogenesis to counteract the hypercaloric state of obesity.

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